Oligonucleotides have been used in various biological and biochemical applications. They have been used as primers and probes for the polymerase chain reaction (PCR), as antisense agents used in target validation, drug discovery and development, as ribozymes, as aptamers, and as general stimulators of the immune system. This widespread use of oligonucleotides has led to an increasing demand for rapid, inexpensive and efficient methods for their synthesis.
Synthetic oligonucleotides are generally prepared through the repeated coupling of nucleoside phosphoramidites to 5′-hydroxyl groups of nucleoside monomers or the free 5′-hydroxyl groups of growing oligomers. A commonly used method to perform oligomer synthesis is the phosphoramidite approach (see for example: Beaucage and Caruthers (1981) Tetrahedron Letters 22:1859-1862; McBride and Caruthers (1983) Tetrahedron Letters 24:245-248; Sinha et al. (1984) Nucleic Acids Res. 12:4539-4557 and Beaucage and Iyer (1992) Tetrahedron 48:2223-2311, each of which is incorporated herein by reference in its entirety).